ライフサイエンスコーパス: dUTPase

1 dUTPase genes were cloned and expressed from two other c

2 dUTPase is a ubiquitous and essential enzyme responsible

3 dUTPase is an enzyme essential for depleting potentially

4 dUTPase is encoded as an auxiliary gene in a number of v

5 dUTPase, which eliminates dUTP from the DNA biosynthetic

6 dUTPases catalyze the hydrolysis of dUTP into dUMP and p

7 dUTPases convert dUTP to dUMP, thus avoiding the misinco

8 mperature optimum (37 degrees C) than PBCV-1 dUTPase (50 degrees C).

9 o dUTPases have similar properties to PBCV-1 dUTPase except that IL-3A dUTPase has a lower temperatur

10 In type 1 dUTPases, Stl binding is inhibited by dUTP.

11 includes three distinct enzyme families: (1) dUTPases in trypanosomatides, C.jejuni and several other

12 we show that varphiNM1 dut encodes a type 2 dUTPase (DutNM1), which has an alpha-helical structure t

13 The IL-3A dUTPase differs from the PBCV-1 enzyme by nine amino aci

14 operties to PBCV-1 dUTPase except that IL-3A dUTPase has a lower temperature optimum (37 degrees C) t

15 P45 was shown to function as a dUTPase, converting dUTP to dUMP and inorganic pyrophosp

16 roducts, bacterial genes and, in one case, a dUTPase from a eukaryotic virus.

17 Many DNA viruses and retroviruses encode a dUTPase or uracil-DNA glycosylase (UNG) to counteract ur

18 zyme activity were then lost, resulting in a dUTPase containing a single active site with different e

19 The ORF54-encoded protein is a dUTPase; however, dUTPase activity is neither necessary

20 enzymatically active and immunoreacts with a dUTPase-specific monoclonal antibody.

21 es have evolved from an ancestral adenovirus dUTPase and, from this structural framework, developed n

22 o assess the involvement of dUTP binding and dUTPase activity in derepression by DutNM1.

23 Although dCTP deaminase and dUTPase activities are usually found in separate but hom

24 a combined deficiency of exonuclease III and dUTPase, which has been attributed to unrepaired abasic

25 r detectable enzymatic activity, E4 ORF1 and dUTPase proteins were predicted to possess strikingly si

26 nal similarity was found for the E4 ORF1 and dUTPase proteins, we propose that human adenovirus E4 OR

27 ne with the lack of thymidylate synthase and dUTPase in the parasite, which makes deoxy-UMP a dead-en

28 In vivo, archaeal dUTPases may play an essential role in preventing dUTP i

29 alpha fold and are unrelated to the all-beta dUTPases of the majority of organisms including eukaryot

30 tissues and examined the association between dUTPase expression and response to 5-fluorouracil (5-FU)

31 To examine the association between dUTPase expression and response to 5-FU-based chemothera

32 that the relative expression levels of both dUTPase and uracil-DNA glycosylase can have great influe

33 Both dUTPases can interact with the SaPIbov1 Stl master repre

34 pabilities that is specifically activated by dUTPase.

35 The nucleotide pool cleanser dUTPase is highly expressed in CRC and is an attractive

36 molecular replacement using Escherichia coli dUTPase as search model.

37 Crystallized single-copy dUTPases have been shown to assemble as homotrimers.

38 Variable cytoplasmic dUTPase expression was observed in these tumors; however

39 tive bacteria and their phages, and (3) dCTP/dUTPases in enterobacterial T4-like phages.

40 e proteins: dihydrofolate reductase, dCTPase-dUTPase, deoxyribonucleoside monophosphokinase, ribonucl

41 e, aerobic ribonucleotide reductase, dCTPase-dUTPase, gene 32 single-strand DNA-binding protein, and

42 icant similarity to bacterial dCTP deaminase/dUTPase and DNA flavoprotein, respectively.

43 Structure-guided analysis of the new dimeric dUTPase family revealed its sequence relationship to the

44 mechanism of dUTP/dUDP hydrolysis by dimeric dUTPases.

45 representative of the new family of dimeric dUTPases to be structurally characterised.

46 TP pyrophosphatases, suggesting that dimeric dUTPases evolved from a tetrameric MazG-like ancestor by

47 Therefore, dimeric dUTPases can be considered as candidate drug targets.

48 umerous X-ray crystal structures of distinct dUTPase and nucleoside phosphate complexes, which report

49 That two structurally distinct dUTPases bind the same repressor led us to speculate tha

50 lpha and phiNM1 encode structurally distinct dUTPases, Dut80alpha (type 1) and DutNM1 (type 2).

51 l observation that oxaliplatin downregulates dUTPase expression may provide a mechanistic basis contr

52 onstrate a role for E2F-1 and Sp1 in driving dUTPase expression.

53 We show how duplicated dUTPases might fold into a monomer, and we hypothesize t

54 Nucleotide pool sanitizing enzymes Dut (dUTPase), RdgB (dITPase), and MutT (8-oxo-dGTPase) of Es

55 a recombinant expressing VP5 from an early (dUTPase) or another leaky-late (VP16) promoter exhibited

56 re deleted and replaced with a strong early (dUTPase), an equal-strength leaky-late (VP16), or a stri

57 ance and should be of general relevance.EIAV dUTPase is a homotrimer where each subunit folds into a

58 erived macrophages with the anti-EBV-encoded dUTPase Ab 7D6 or the anti-TLR2 Ab blocked the productio

59 we demonstrate that the purified EBV-encoded dUTPase activates NF-kappaB in a dose-dependent manner t

60 naling pathways activated by the EBV-encoded dUTPase and to determine its role in modulating immune r

61 was abrogated by anti-TLR2, anti-EBV-encoded dUTPase blocking Abs and the overexpression of a dominan

62 However, the role of EBV-encoded dUTPase in DC activation/function and its potential cont

63 onocyte-derived macrophages with EBV-encoded dUTPase induces the expression of proinflammatory cytoki

64 importantly, we demonstrate that EBV-encoded dUTPase is secreted in exosomes from chemically induced

65 these findings suggest that the EBV-encoded dUTPase may act as an intercellular signaling molecule c

66 eome array studies revealed that EBV-encoded dUTPase modulates DC immune responses by inducing the se

67 esent study, we demonstrate that EBV-encoded dUTPase significantly altered the expression of genes in

68 nd neutralizing antibody against EBV-encoded dUTPase were compared in the three patient groups.

69 er, the receptor responsible for EBV-encoded dUTPase-mediated biological effects is not known.

70 DCs) may also be a target of the EBV-encoded dUTPase.

71 ed the production of IL-6 by the EBV-encoded dUTPase.

72 at the trimeric staphylococcal phage encoded dUTPases (Duts) are signaling molecules that act analogo

73 The trimeric staphylococcal phage-encoded dUTPases (Duts) are signalling molecules that induce the

74 The 5' region of the gene encoding dUTPase was isolated and characterized by a combination

75 criptional link between the essential enzyme dUTPase and the tumor suppressor p53.

76 kidney tsA201 cells, transiently expressing dUTPase showed that this protein is present predominantl

77 in vitro demonstrates that the P. falciparum dUTPase constitutes a valid and attractive novel target

78 ools for further investigating P. falciparum dUTPase for the development of much-needed novel antimal

79 nd selective inhibitors of the P. falciparum dUTPase that show drug-like properties and represent goo

80 ounds were assayed against both P.falciparum dUTPase and intact parasites.

81 Pase vs. 249 +/- 70 pg/mL in SA negative for dUTPase antibody).

82 ng an AMI and who were antibody positive for dUTPase (ANOVA p=0.008; 369 +/- 183 pg/mL in AMI and pos

83 8; 369 +/- 183 pg/mL in AMI and positive for dUTPase vs. 249 +/- 70 pg/mL in SA negative for dUTPase

84 activity mutants were created and tested for dUTPase activity using a novel NMR-based assay.

85 lted in a coding region comprising two fused dUTPase domains.

86 the human adenovirus E4 ORF1s, was a genuine dUTPase enzyme.

87 The recombinant protein has dUTPase activity and requires Mg(2+) for optimal activit

88 onal genes were derived from the herpesvirus dUTPase gene, probably by duplication.

89 ing a protein that is related to herpesvirus dUTPases but has a different and as yet unrecognized fun

90 CD4+ T cells, because these cells have high dUTPase activity (low dUTP), and only modest levels of h

91 DCD-DUT is a hexamer, unlike the homologous dUTPases, and its subunits contain several insertions an

92 ORF54-encoded protein is a dUTPase; however, dUTPase activity is neither necessary nor sufficient for

93 predicted amino-terminal sequence for human dUTPase.

94 nuclear and mitochondrial isoforms of human dUTPase.

95 zyme, which exhibits 92% identity with human dUTPase; the N-terminal extra 62-amino acid residue regi

96 erfamilies: MutT-related (Nudix) hydrolases, dUTPase, ITPase (Maf/HAM1) and all-alpha NTP pyrophospha

97 resents the first clinical study implicating dUTPase overexpression as a mechanism of resistance to T

98 upport the idea that small loop movements in dUTPase allow the shuttlingof the nucleotides between th

99 his hidden pocket and product is released in dUTPases is unresolved because of conflicting crystallog

100 dut-1 defect in Escherichia coli inactivates dUTPase, causing increased uracil incorporation in DNA a

101 Homologues of the C.jejuni dUTPase have been identified in several other bacteria a

102 The X-ray structure of the C.jejuni dUTPase in complex with the non-hydrolysable substrate a

103 These data support HERV-K dUTPase as a potential contributor to psoriasis pathophy

104 ntibody responses against recombinant HERV-K dUTPase in psoriasis patients compared with controls (P<

105 en conducted to determine the role of HERV-K dUTPase in psoriasis.

106 a support an independent role for the HERV-K dUTPase on psoriasis susceptibility, and suggest the nee

107 her T-cell responses against a single HERV-K dUTPase peptide (P<0.05).

108 demonstrate that wild-type and mutant HERV-K dUTPase proteins induce the activation of NF-kappaB thro

109 imary cells with wild-type and mutant HERV-K dUTPase proteins triggered the secretion of T(H)1 and T(

110 fter adjusting the association of the HERV-K dUTPase variants for the potential confounding effects o

111 and case-control association study of HERV-K dUTPase variants in 708 psoriasis cases and 349 healthy

112 Five common HERV-K dUTPase variants were found to be highly associated with

113 For this purpose, we constructed an HERV-K dUTPase wild-type sequence, as well as specific mutation

114 d the human endogenous retrovirus K (HERV-K) dUTPase located within the PSORS1 locus in the major his

115 dUDP binding not observed in the other known dUTPase structures.

116 [32P]Orthophosphate-labeled dUTPase was purified from HeLa cells, revealing that onl

117 ant and wild-type forms of p53 in modulating dUTPase promoter activity.

118 The in silico data further revealed a new dUTPase conformation on the pathway to a relatively open

119 Nuclear dUTPase staining within these tumors was also associated

120 Of the patients lacking nuclear dUTPase expression, 6 responded to 5-FU-based chemothera

121 ates that low intratumoral levels of nuclear dUTPase protein expression is associated with response t

122 Conversely, high levels of nuclear dUTPase protein expression predict for tumor resistance

123 s with tumors demonstrating positive nuclear dUTPase expression (P = 0.09).

124 Of the patients presenting positive nuclear dUTPase expression, 0 responded to chemotherapy, 1 had s

125 In normal tissues, nuclear dUTPase staining was observed exclusively in replicating

126 erium tuberculosis dUTP nucleotidohydrolase (dUTPase) has been determined at 1.3 Angstrom resolution

127 dUTP nucleotidohydrolase (dUTPase) is the key regulator of dUTP pools, and signifi

128 oxyuridine triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis of dUTP to dUMP and PP

129 oxyuridine triphosphate nucleotidohydrolase (dUTPase) encoded by a human endogenous retrovirus K (HER

130 uridine 5'-triphosphate nucleotidohydrolase (dUTPase) from parasitic protozoa.

131 oxyuridine triphosphate nucleotidohydrolase (dUTPase) modulates innate immunity in human primary mono

132 uridine 5'-triphosphate nucleotidohydrolase (dUTPase), an enzyme involved in nucleotide metabolism th

133 oxyuridine triphosphate nucleotidohydrolase (dUTPase), produced following reactivation of Epstein Bar

134 oxyuridine triphosphate nucleotidohydrolase (dUTPase; EC 3.6.1.23) was purified from HeLa cells by im

135 The activities of dUTPase and uracil-DNA glycosylase, key enzymes in uraci

136 A comprehensive analysis of dUTPase amino acid sequence relationships was performed

137 phosphorylated, a more in depth analysis of dUTPase phosphorylation was undertaken.

138 e site of attack and shows the capability of dUTPase to cleave the dUTP analogue alpha,beta-imido-dUT

139 In contrast, depletion of dUTPase activity leads to the accumulation of dUTP pools

140 In contrast, depletion of dUTPase in HT29 cells did not substantially affect chemo

141 Thus, immunohistochemical detection of dUTPase in colon cancers provides distinct intracellular

142 -dependent transcriptional downregulation of dUTPase not observed in the isogenic null cell line.

143 blished work has indicated that evolution of dUTPase in the class of herpesviruses that infect mammal

144 ndent In contrast, cytoplasmic expression of dUTPase does not correlate with proliferation status and

145 uorouracil (5-FU) and elevated expression of dUTPase is negatively correlated with clinical response

146 colon cancer tumor specimens, expression of dUTPase was shown to be highly variable in both amount a

147 cate that the lower molecular weight form of dUTPase (DUT-N) is associated with the nucleus, while th

148 Each form of dUTPase has a distinct cellular localization.

149 lls, revealing that only the nuclear form of dUTPase is phosphorylated.

150 these data suggest that the nuclear form of dUTPase may be a target for cyclin-dependent kinase phos

151 n subunit association of the nuclear form of dUTPase.

152 hese analyses indicate that the two forms of dUTPase are largely identical, differing only in a short

153 ite the structural difference, both forms of dUTPase exhibited identical binding characteristics for

154 e gel electrophoresis, two distinct forms of dUTPase were evident in the purified preparation.

155 The identification of dUTPase as a PPAR-interacting protein suggests a possibl

156 tion and indicate that partial inhibition of dUTPase is a viable therapeutic approach to enhance the

157 this work and determine if both isoforms of dUTPase are phosphorylated, a more in depth analysis of

158 stinct nuclear and mitochondrial isoforms of dUTPase in human cells, reporting the cDNA sequence of t

159 port, we identified two distinct isoforms of dUTPase in human cells.

160 ibroblast cells which have reduced levels of dUTPase expression.

161 termined the effects of decreasing levels of dUTPase on sensitivity to the thymidylate synthase (TS)

162 proteins lacked conserved protein motifs of dUTPase enzymes or detectable enzymatic activity, E4 ORF

163 e have determined the expression patterns of dUTPase in normal and neoplastic tissues and examined th

164 Patterns of dUTPase protein expression observed included exclusive n

165 placement with Ala blocks phosphorylation of dUTPase in vivo.

166 To validate the potential of dUTPase as a target for drug development, we used small

167 The X-ray structures of dUTPase from equine infectious anaemia virus (EIAV) in u

168 The suppression of dUTPase by oxaliplatin promoted increased levels of dUTP

169 Suppression of dUTPase in SW620 and MCF-7 cells resulted in a significa

170 onal differences between arginine fingers of dUTPases and NTPases are explained on the basis of the u

171 RC cell line, a cell line that overexpresses dUTPase; compared to HT29 CRC cells and NCTC-929 fibrobl

172 Cells overexpressing dUTPase were protected from cytotoxicity by their abilit

173 Pfu dUTPase improves the yield of products amplified with Pf

174 ination of cloned Pfu DNA polymerase and Pfu dUTPase (PfuTurbo DNA polymerase) can amplify longer tar

175 other Gram-negative bacteria, (2) predicted dUTPases in various Gram-positive bacteria and their pha

176 pro-inflammatory action of the early protein dUTPase that is produced even during incomplete viral re

177 cellular enveloped virus host range protein, dUTPase, hydroxysteroid dehydrogenase, superoxide dismut

178 L8, pUL20, pUL32, pUL40 (RR2), pUL42, pUL50 (dUTPase), and Rsp40/ICP22.

179 e chemistry performed by the pyrophosphatase dUTPases.

180 f organismal and viral dUTP pyrophosphatase (dUTPase) enzymes.

181 oviruses either encode dUTP pyrophosphatase (dUTPase) or package host-derived uracil DNA glycosylase

182 inant Escherichia coli dUTP pyrophosphatase (dUTPase), an essential enzyme preventing incorporation o

183 Full-length rat dUTPase prevents PPAR-retinoid X receptor heterodimeriza

184 the N-terminal 62-amino acid segment of rat dUTPase.

185 In vitro binding assays indicate that rat dUTPase interacts with all three isoforms of mouse PPAR,

186 Northern blot hybridization shows that rat dUTPase is encoded by an abundant 1kilobase mRNA species

187 re, using the Mason-Pfizer monkey retrovirus dUTPase, we study the dUTPase-catalyzed hydrolysis of dU

188 pping arginine-rich motifs, and a C-terminal dUTPase-like structure.

189 utNM1 is active in Stl derepression and that dUTPase activity is not necessary for the mobilization o

190 ious work, this laboratory demonstrated that dUTPase is posttranslationally phosphorylated on serine

191 the same repressor led us to speculate that dUTPase activity may be important to the derepression pr

192 Recent evidence suggests that dUTPases may also represent a selective drug target in m

193 n treatment induced enrichment of p53 at the dUTPase promoter with a concomitant reduction in Sp1.

194 e such SaPI, SaPIbov1, is derepressed by the dUTPase (Dut) of bacteriophage 80alpha (Dut80alpha) and

195 ound that recombinant viruses containing the dUTPase promoter inserted in the VP5 locus expressed VP5

196 uencing a 4,245-bp region which contains the dUTPase gene, part of a putative spliced DNA polymerase

197 ertions and substitutions different from the dUTPase beta barrel core that likely contribute to dCTP

198 (chr15.hg19:g.48,626,619A>G) located in the dUTPase (DUT) gene (National Center for Biotechnology In

199 o and in vitro, leading to inhibition of the dUTPase activity and Stl release from its target DNA.

200 The crystal structure of the dUTPase from the important gastric pathogen Campylobacte

201 the first functional characterization of the dUTPase promoter and demonstrate a role for E2F-1 and Sp

202 Combining mass spectrometry analysis of the dUTPase-catalyzed reaction carried out in and quantum me

203 e-rRNA levels, and this was dependent on the dUTPase-like motif in pUL31.

204 uctural and biochemical methods to study the dUTPase from Mycobacterium tuberculosis In particular, t

205 izer monkey retrovirus dUTPase, we study the dUTPase-catalyzed hydrolysis of dUTP, an incorrect DNA b

206 EBV infection, our results suggest that the dUTPase could be a potential target for the development

207 These analyses demonstrate that the dUTPase isoforms are encoded by the same gene with isofo

208 C-terminal region different from that of the dUTPases and possible mechanisms for both bifunctional e

209 A comparison of the dUTPases from C.jejuni and Trypanosoma cruzi reveals a c

210 ditional studies to clarify the role of this dUTPase in the pathogenesis of psoriasis.

211 f the active centre established for trimeric dUTPase structures, in which subunit interfaces form thr

212 of a conserved arginine residue in trimeric dUTPases that meets all the criteria established for arg

213 A putative deoxyuridine triphosphatase (dUTPase) gene from chlorella virus PBCV-1 was cloned, an

214 identified rat deoxyuridine-triphosphatase (dUTPase, EC 3.6.1.23) as a PPARalpha-interacting protein

215 monomer, and we hypothesize that triplicated dUTPases also assemble as monomers.

216 g a specific inhibitor of the M.tuberculosis dUTPase enzyme.

217 been proposed that inhibiting M.tuberculosis dUTPase might be an effective means to treat tuberculosi

218 The two dUTPases have similar properties to PBCV-1 dUTPase excep

219 d in complex with two structurally unrelated dUTPases from different S. aureus phages.

220 enetic analysis revealed at least five viral dUTPase sequence lineages in well-supported monophyletic

221 ows that tegument protein VP22 and the viral dUTPase, encoded by genes UL49 and UL50, respectively, a

222 PPARalpha when PPARalpha is coexpressed with dUTPase.

223 content was increased, Pfu formulations with dUTPase exhibited significantly higher efficiencies than

224 Interaction of PPARalpha with dUTPase is with the N-terminal 62-amino acid segment of

225 repair transactions cannot be redundant with dUTPase and instead reveal "defect-damage-repair" cycles